U.S. patent application number 14/362908 was filed with the patent office on 2014-10-16 for aqueous oral care compositions.
This patent application is currently assigned to Colgate-Palmolive Company. The applicant listed for this patent is Davide Miksa, Shira Pilch, Paloma Pimenta, Aarti Rege, Richard Sullivan. Invention is credited to Davide Miksa, Shira Pilch, Paloma Pimenta, Aarti Rege, Richard Sullivan.
Application Number | 20140305461 14/362908 |
Document ID | / |
Family ID | 45491772 |
Filed Date | 2014-10-16 |
United States Patent
Application |
20140305461 |
Kind Code |
A1 |
Pimenta; Paloma ; et
al. |
October 16, 2014 |
AQUEOUS ORAL CARE COMPOSITIONS
Abstract
Described herein are aqueous oral care compositions comprising
(a) an effective amount of a basic amino acid in free or orally
acceptable salt form; and (b) a polymer system comprising (i) a
cellulosic polymer, (ii) a gum polymer, and (iii) a polyacrylate
polymer or co-polymer; and methods of making and using the
same.
Inventors: |
Pimenta; Paloma; (Staten
Island, NY) ; Miksa; Davide; (Doylestown, PA)
; Pilch; Shira; (Highland Park, NJ) ; Rege;
Aarti; (East Windsor, NJ) ; Sullivan; Richard;
(Atlantic Highlands, NJ) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Pimenta; Paloma
Miksa; Davide
Pilch; Shira
Rege; Aarti
Sullivan; Richard |
Staten Island
Doylestown
Highland Park
East Windsor
Atlantic Highlands |
NY
PA
NJ
NJ
NJ |
US
US
US
US
US |
|
|
Assignee: |
Colgate-Palmolive Company
New York
NY
|
Family ID: |
45491772 |
Appl. No.: |
14/362908 |
Filed: |
December 15, 2011 |
PCT Filed: |
December 15, 2011 |
PCT NO: |
PCT/US2011/065125 |
371 Date: |
June 4, 2014 |
Current U.S.
Class: |
132/200 ; 424/52;
424/54 |
Current CPC
Class: |
A61K 8/73 20130101; A61K
8/44 20130101; A61K 8/21 20130101; A61K 8/8152 20130101; A61Q 11/00
20130101; A61K 2800/594 20130101; A61K 8/731 20130101 |
Class at
Publication: |
132/200 ; 424/54;
424/52 |
International
Class: |
A61K 8/81 20060101
A61K008/81; A61K 8/44 20060101 A61K008/44; A61K 8/21 20060101
A61K008/21; A61Q 11/00 20060101 A61Q011/00 |
Claims
1. An aqueous oral care composition comprising a) an effective
amount of a basic amino acid in free or orally acceptable salt
form; and b) a polymer system comprising (i) a cellulosic polymer,
(ii) a gum polymer, and (iii) a polyacrylate polymer or
co-polymer.
2. The composition of claim 1, further comprising a fluoride
source; wherein the fluoride source is present in an amount
effective to provide from about 90 to about 500 ppm of
fluoride.
3. The composition of claim 2, wherein the fluoride source is
present in an amount effective to provide about 225 ppm of
fluoride.
4. The composition of claim 1, wherein the fluoride source is
selected from sodium fluoride; sodium monofluorophosphate; and a
combination thereof.
5. The composition of claim 1, wherein the fluoride source
comprises sodium fluoride.
6. The composition of claim 1 wherein the basic amino acid
comprises L-arginine in free or orally acceptable salt form.
7. The composition of claim 1 claim wherein the effective amount of
the basic amino acid in free or orally acceptable salt form
comprises 0.05 to 2% by weight of the formulation (measured as the
weight of the free base equivalent when in orally acceptable salt
form).
8. The composition of claim 1, further comprising a buffering
agent.
9. The composition of claim 1, further comprising a humectant.
10. The composition of claim 1, further comprising an antibacterial
agent.
11. The composition of claim 1 wherein the cellulosic polymer is
selected from a hydroxyalkyl methyl cellulose; a carboxyalkyl
methylcellulose; a hydroxyalkyl cellulose; an alkyl cellulose; a
carboxyalkyl cellulose, and a combination of two or more
thereof.
12. The composition of claim 1 wherein the cellulosic polymer
comprises carboxymethyl cellulose.
13. The composition of claim 1 wherein the gum polymer is selected
from carrageenan gum, xanthan gum, and combinations thereof.
14. The composition of claim 1 wherein the polyacrylate polymer or
co-polymer is a carbomer.
15. The composition of claim 1 wherein the polyacrylate polymer or
co-polymer is selected from homo- and copolymers of acrylic acid
crosslinked with a polyalkenyl polyether.
16. The aqueous oral care composition of claim 1 comprising: a)
from about 0.5% to about 2%, by weight, of a basic amino acid in
free or orally acceptable salt form; b) a polymer system comprising
(i) a cellulosic polymer, (ii) a gum polymer, and (iii) a
polyacrylate polymer or co-polymer; and c) from about 0.01 to about
0.5%, by weight, or a fluoride source; wherein the composition
delivers an amount of fluoride effective to provide a step height
difference of less than 0.25 microns, when evaluated using the
Hooper protocol.
17. The composition of claim 16, wherein the fluoride source is
present in the amount of about 0.05%, by weight, of the
composition.
18. The composition of claim 1, wherein the composition has a flow
rate index of less than 0.85.
19. The composition of claim 1, wherein the composition has a
G'/G'' ratio of greater than or equal to 0.5.
20. A method of reducing dental enamel erosion comprising
administering a composition according to claim 1 to the oral cavity
of subject in need thereof.
21. The method of claim 20, wherein the administering comprises
rinsing for from about 15 to about 60 seconds.
22. The composition of claim 1 for use in a method of reducing
dental enamel erosion.
23. The composition of claim 22 wherein the method comprises
administering the composition to the oral cavity of a subject in
need thereof.
24. The composition of claim 23 wherein the method further
comprises rinsing for from about 15 to about 60 seconds.
Description
BACKGROUND
[0001] Conventional mouthwash products may contain antibacterial
agents and/or fluoride, but they generally do not prevent or repair
the acid channels, or enhance the delivery and retention of active
agents. Efficacious protection against such acid attacks to the
tooth surface should ideally provide a physical barrier against the
acid attack, as well as enhance delivery and retention of an active
agent that can neutralize the acid and/or strengthen the tooth
enamel.
SUMMARY
[0002] In some embodiments, the present invention provides an
aqueous oral care composition comprising an effective amount of a
basic amino acid, in free or orally acceptable salt form, and a
polymer system comprising (i) a cellulosic polymer, (ii) a gum
polymer, and (iii) a polyacrylate polymer or co-polymer, e.g.,
wherein the mouthwash displays (i) a measurable degree of
viscoelasticity with a ratio of elastic to viscous components,
G'/G'', greater than 0.5 and (ii) shear thinning behavior with a
flow rate index, n, of less than 0.85. In some embodiments, the
composition is a viscoelastic mouthwash. In some embodiments, the
mouthwash optionally further comprises an effective amount of a
fluoride source.
[0003] The high viscoelasticity of the formulation (G'/G''>0.5)
favors the formation of a polymer film on the tooth surface and
greater retention of actives such as fluoride, arginine or
buffering agents onto the enamel surface. The shear thinning
property (n<0.85) further characterizes the mouthwash as
viscoelastic and non-Newtonian and helps drive the consumer
acceptability of the mouthwash.
[0004] As demonstrated by the examples below, the compositions of
the present invention provide improved resistance to enamel
erosion. Without being bound by theory, it is believed that the use
of mucoadhesive polymers at concentrations sufficient for the
polymers to overlap significantly and form a network in solution
results in the deposition of a polymer film on hard and soft
tissues of the oral cavity upon usage. This polymer film serves as
a physical barrier against erosive acids, as well as a carrier to
enhance the delivery and retention of fluoride and/or basic amino
acids such as arginine onto enamel surfaces, therefore providing
superior enamel protection against acid induced erosion and
demineralization. Moreover, it is believed that the uptake of the
basic amino acid, e.g., arginine, is enhanced because basic amino
acids such as arginine are positively charged. In the presence of a
polymer network that is largely negative charged, the charge and
charge interaction enhances the deposition of the basic amino acid
to oral surfaces.
[0005] Further areas of applicability of the present invention will
become apparent from the detailed description provided hereinafter.
It should be understood that the detailed description and specific
examples, while indicating the preferred embodiment of the
invention, are intended for purposes of illustration only and are
not intended to limit the scope of the invention.
DETAILED DESCRIPTION
[0006] The following description of the preferred embodiment(s) is
merely exemplary in nature and is in no way intended to limit the
invention, its application, or uses.
[0007] Some embodiments of the present invention provide an aqueous
oral care composition comprising an effective amount of a basic
amino acid in free or orally acceptable salt form and; a polymer
system comprising (i) a cellulosic polymer, (ii) a gum polymer, and
(iii) a polyacrylate polymer or co-polymer; wherein the composition
has a flow rate index of less than 0.85.
[0008] Some embodiments further comprise a fluoride source; wherein
the fluoride source. In some embodiments, the fluoride source is
present in an amount effective to provide from about 90 to about
500 ppm of fluoride. In other embodiments, the fluoride source is
present in an amount effective to provide about 225 ppm of
fluoride.
[0009] In some embodiments, the fluoride source is selected from
stannous fluoride, sodium fluoride, potassium fluoride, sodium
monofluorophosphate, sodium fluorosilicate, ammonium
fluorosilicate, amine fluoride (e.g.,
N'-octadecyltrimethylendiamine-N,N,N'-tris(2-ethanol)-dihydrofluoride),
ammonium fluoride, titanium fluoride, hexafluorosulfate, and a
combination of two or more thereof.
[0010] In some embodiments, the fluoride source is selected from
sodium fluoride; sodium monofluorophosphate; and a combination
thereof. In other embodiments, the fluoride source comprises sodium
fluoride.
[0011] In some embodiments, the basic amino acid comprises
L-arginine in free or orally acceptable salt form. In some
embodiments, the basic amino acid is selected from arginine free
base, arginine hydrochloride, arginine phosphate, arginine
bicarbonate, and combinations thereof. In some embodiments, the
effective amount of the basic amino acid in free or orally
acceptable salt form comprises 0.05 to 2% by weight of the
formulation (measured as the weight of the free base equivalent
when in orally acceptable salt form).
[0012] Some embodiments further comprise a buffering agent. In some
embodiments, the buffering agent is a sodium phosphate buffer
(e.g., sodium phosphate monobasic and disodium phospate).
[0013] Other embodiments further comprise a humectant, e.g.,
selected from glycerin, sorbitol, propylene glycol, and a
combination of two or more thereof.
[0014] Still other embodiments further comprise an antibacterial
agent, e.g., triclosan or cetylpyridinium chloride.
[0015] The composition of any of the foregoing claims wherein the
cellulosic polymer is selected from a hydroxyalkyl methyl
cellulose; a carboxyalkyl methylcellulose; a hydroxyalkyl
cellulose; an alkyl cellulose; a carboxyalkyl cellulose, and a
combination of two or more thereof.
[0016] Some embodiments provide an aqueous oral care composition
comprising: from about 0.5% to about 2%, by weight, of a basic
amino acid in free or orally acceptable salt form; a polymer system
comprising (i) a cellulosic polymer, (ii) a gum polymer, and (iii)
a polyacrylate polymer or co-polymer; and from about 0.01 to about
0.5%, by weight, of a fluoride source; wherein the composition has
a flow rate index of less than 0.85; and wherein the composition
delivers an amount of fluoride effective to provide a step height
difference of less than 0.25 microns, when evaluated using the
Hooper protocol.
[0017] In some embodiments, the fluoride source is present in an
amount from about 0.02% to about 0.2%, by weight, of the
composition. In some embodiments, the fluoride source is present in
an amount from about 0.03% to about 0.08%, by weight, of the
composition. Other embodiments provide a composition wherein the
fluoride source is present in the amount of about 0.05%, by weight,
of the composition. In some embodiments, the fluoride source is
present in the amount of 0.5%, by weight, of the composition.
[0018] Some embodiments of the present invention provide a method
of reducing dental enamel erosion comprising administering any one
of the compositions described herein to the oral cavity of subject
in need thereof. In some embodiments, the administering comprises
rinsing for from about 15 to about 60 seconds. In some embodiments,
the administering comprises rinsing for from about 30 seconds.
[0019] Some embodiments of the present invention thus provide, a
viscoelastic mouthwash (Mouthwash 1) comprising (a) an effective
amount of a basic amino acid in free or orally acceptable salt form
and (b) a polymer system comprising (i) a cellulosic polymer, (ii)
a gum polymer, and (iii) a polyacrylate polymer or co-polymer.
[0020] In some embodiments, the cellulosic polymer is selected from
hydroxyalkyl methyl celluloses (such as hydroxypropyl methyl
cellulose, hydroxybutyl methyl cellulose, hydroxyethyl methyl
cellulose, hydroxymethyl methyl cellulose and hydroxyethylpropyl
methyl cellulose); carboxyalkyl methylcelluloses (such as
carboxypropyl methyl cellulose, carboxybutyl methyl cellulose,
carboxyethyl methyl cellulose, carboxymethyl methyl cellulose and
carboxyethylpropyl methyl cellulose); hydroxyalkyl celluloses (such
as hydroxypropyl cellulose, hydroxybutyl cellulose, hydroxyethyl
cellulose, hydroxymethyl cellulose and hydroxyethylpropyl
cellulose); alkyl celluloses (such as propyl cellulose, butyl
cellulose, ethyl cellulose, methyl cellulose); carboxyalkyl
celluloses (such as carboxypropyl cellulose, carboxybutyl
cellulose, carboxyethyl cellulose, carboxymethyl cellulose and
carboxyethylpropyl cellulose), and combinations thereof.
[0021] In some embodiments, the cellulosic polymer comprises
carboxymethyl cellulose.
[0022] In some embodiments, the gum polymer is selected from
carrageenan gum, xanthan gum, and combinations thereof. In some
embodiments, the gum polymer comprises xanthan gum. In some
embodiments, the polyacrylate polymer or co-polymer is a carbomer.
In some embodiments, the polyacrylate polymer or co-polymer is
selected from homo- and copolymers of acrylic acid crosslinked with
a polyalkenyl polyether.
[0023] In some embodiments, the compositions comprise the
ingredients in the concentration ranges provided in Table 1
(below).
TABLE-US-00001 TABLE 1 Conc. Range Ingredient % wt/wt Water
50.0-90.0 Humectants 1.0-25.0 Surfactant 0.01-10.0 Sodium phosphate
monobasic 0.01-5.0 Disodium phosphate 0.01-5.0 Preservative
0.01-1.0 Flavor 0.01-1.0 Cellulosic polymer 0.01-0.5 Gum polymer
0.01-0.5 Polyacrylate polymer or co-polymer 0.01-0.5 Sodium
fluoride 0-0.05 Arginine (in free or salt form, by weight of the
free base) 0.05-2.0 Sweetener 0.001-0.5 Cetylpyridinium chloride
0.001-1.0
[0024] Viscoelastic mouthwash formulations are described in the
following co-pending applications PCT/US 2010/061962, PCT/US
2010/061956, and PCT/US 2010/061959, all filed Dec. 23, 2010, the
contents of which are incorporated herein by reference in their
entirety.
[0025] The compositions of the present invention are carefully
tailored with the right combination and concentration of polymers
to form a viscoelastic, low viscosity aqueous solution that possess
unique rheology but still resembles the fluidity of a typical
mouthwash.
[0026] As used herein, the term "viscoelastic fluid" refers to a
complex fluid that exhibits mechanical properties that are both
elastic (solid-like e.g. rubber) and viscous (liquid-like, flowable
e.g. water). A viscoelastic fluid composition will deform and flow
under the influence of an applied shear stress (e.g. shaking or
swishing in the mouth), but when the stress is removed the
composition will recover from the deformation. The elastic portion
of the viscoelastic behavior is quantified by the elastic modulus
(G'), while the viscous portion is quantified by the viscous
modulus (G'').
[0027] As used herein, the term "shear thinning" refers to a
property in which viscosity decreases with increasing rate of shear
stress. Materials that exhibit shear thinning properties are called
pseudoplastic.
[0028] As used herein, "structured fluid" and "structured
composition" may be used interchangeably, and refer to a fluid that
exhibits a G' value greater than the G'' value (i.e. the ratio of
G' to G'' is >0.5) within the linear viscoelastic region of a
strain sweep measurement. The ratio of G' to G'' has been
identified as the Structural Parameter.
[0029] The basic amino acids which can be used in the compositions
of the present invention include not only naturally occurring basic
amino acids, such as arginine, lysine, and histidine, but also any
basic amino acids having a carboxyl group and an amino group in the
molecule. Accordingly, basic amino acids include, but are not
limited to, arginine, lysine, citrullene, ornithine, creatine,
histidine, diaminobutanoic acid, diaminoproprionic acid, salts
thereof or combinations thereof. In a particular embodiment, the
basic amino acids are selected from arginine, citrullene, and
ornithine, preferably, arginine, for example, L-arginine.
[0030] The compositions of the invention are intended for topical
use in the mouth and so salts for use in the present invention
should be orally acceptable, that is, safe for topical use in the
mouth, in the amounts and concentrations provided. Suitable salts
include salts known in the art to be pharmaceutically acceptable
salts, which are generally considered to be orally acceptable for
this purpose in the amounts and concentrations provided. Orally
acceptable salts include those derived from pharmaceutically
acceptable inorganic or organic acids or bases, for example acid
addition salts formed by acids which form a physiological
acceptable anion, e.g., hydrochloride salt, and base addition salts
formed by bases which form a physiologically acceptable cation, for
example those derived from alkali metals such as potassium and
sodium or alkaline earth metals such as calcium and magnesium.
Physiologically acceptable salts may be obtained using standard
procedures known in the art, for example, by reacting a
sufficiently basic compound such as an amine with a suitable acid
affording a physiologically acceptable anion.
[0031] In some embodiments the compositions further comprise one or
more components selected from a fluoride ion source; a tartar
control agent; a buffering agent; an abrasive; and a combination of
two or more thereof. In some embodiments, at least one of the one
or more components is a fluoride ion source selected from: stannous
fluoride, sodium fluoride, potassium fluoride, sodium
monofluorophosphate, sodium fluorosilicate, ammonium
fluorosilicate, amine fluoride, ammonium fluoride, and a
combination of two or more thereof.
[0032] Synthetic high molecular weight polymers of acrylic acid
known as carbomer may be homopolymers of acrylic acid, crosslinked
with an allyl ether pentaerythritol, allyl ether of sucrose or
allyl ether of propylene. Carbomer has a USP classification of
"carbomer homopolymer Type A". Carbomers have the ability to
adsorb, retain water and swell to many times their original volume.
Carbomers codes (910, 934, 940, 941, 971, 974 and 934P) are an
indication of molecular weight and the specific components of the
polymer. Carbomers are commercially available, under the trade name
Carbopol.RTM. from Lubrizol and other companies.
[0033] Humectants useful herein include polyhydric alcohols such as
glycerin, sorbitol, xylitol or low molecular weight PEGs, alkylene
glycol such as polyethylene glycol or propylene glycol. In various
embodiments, humectants are operable to prevent hardening of paste
or gel compositions upon exposure to air. In various embodiments
humectants also function as sweeteners. In some embodiments, the
humectant is present in the amount of about 1 to about 40% each by
weight. In some embodiments, the humectant is sorbitol. In some
embodiments sorbitol present at a concentration of from about 5 to
about 25%, by weight. In some embodiments sorbitol present at a
concentration of from about 5 to about 15%, by weight. In some
embodiments, the sorbitol is present at a concentration of about
10%, by weight. Reference to sorbitol herein refers to the material
typically as available commercially in 70% aqueous solutions. In
some embodiments, the total humectant concentration is from about 1
to about 60%, by weight. In some embodiments, the humectant is
glycerin. In some embodiments, glycerin is present at a
concentration of from about 5 to about 15%, by weight. In some
embodiments, glycerin present is at a concentration of about 7.5%,
by weight. In some embodiments, the humectant is propylene glycol.
In some embodiments, propylene glycol is present at a concentration
of about 5 to about 15%, by weight. In some embodiments, propylene
glycol is present at a concentration of about 7%, by weight.
[0034] Some embodiments provide a composition wherein a
preservative is present. In some embodiments, the preservative is
selected from parabens, potassium sorbate, benzyl alcohol,
phenoxyethanol, polyaminopropryl biguanide, caprylic acid, sodium
benzoate and cetylpyridinium chloride. In some embodiments, the
preservative is present at a concentration of from about 0.0001 to
about 1%, by weight. In some embodiments, the preservative is
present at a concentration of from about 0.01 to about 1%, by
weight. In some embodiments, the preservative is present at a
concentration of about 0.5%, by weight.
[0035] Colorants such as dyes may be food color additives presently
certified under the Food Drug & Cosmetic Act for use in food
and ingested drugs, including dyes such as FD&C Red No. 3
(sodium salt of tetraiodofluorescein), Food Red 17, disodium salt
of
6-hydroxy-5-{(2-methoxy-5-methyl-4-sulphophenyl)azo}-2-n-aphthalenesulfon-
ic acid, Food Yellow 13, sodium salt of a mixture of the mono and
disulphonic acids of quinophtalone or 2-(2-quinolyl) indanedione,
FD&C Yellow No. 5 (sodium salt of
4-p-sulfophenylazo-1-p-sul-fophenyl-5-hydroxypyrazole-3 carboxylic
acid), FD&C Yellow No. 6 (sodium salt of
p-sulfophenylazo-B-naphtol-6-monosulfonate), FD&C Green No. 3
(disodium salt of
4-{[4-(N-ethyl-p-sulfobenzylamino)-phenyl]-(4-hydroxy-2-sulfonium-
phenyl)-methylene}-[1-(N-ethyl-N-p-sulfobenzyl)-.DELTA.-3,5-cycl-ohexadien-
imine], FD&C Blue No. 1 (disodium salt of
dibenzyldiethyl-diamino-triphenylcarbinol trisulfonic acid
anhydrite), FD&C Blue No. 2 (sodium salt of disulfonic acid of
indigotin) and mixtures thereof in various proportions. Typically,
colorants if included are present in very small quantities.
[0036] Flavor agents are known, such as natural and artificial
flavors. These flavorings may be chosen from synthetic flavor oils
and flavoring aromatics, and/or oils, oleo resins and extracts
derived from plants, leaves, flowers, fruits and so forth, and
combinations thereof. Representative flavor oils include: spearmint
oil, cinnamon oil, peppermint oil, clove oil, bay oil, thyme oil,
cedar leaf oil, oil of nutmeg, oil of sage, and oil of bitter
almonds. These flavor agents can be used individually or in
admixture. Commonly used flavors include mints such as peppermint,
artificial vanilla, cinnamon derivatives, and various fruit
flavors, whether employed individually or in admixture. Generally,
any flavoring or food additive, such as those described in
Chemicals Used in Food Processing, publication 1274 by the National
Academy of Sciences, pages 63-258, may be used. Typically,
flavorants if included are present at 0.01-1%, by weight. In some
embodiments, flavoring may be present in about 0.2%, by weight.
[0037] Sweeteners include both natural and artificial sweeteners.
Suitable sweetener include water soluble sweetening agents such as
monosaccharides, disaccharides and poysaccharides such as xylose,
ribose, glucose (dextrose), mannose, galactose, fructose
(levulose), sucrose (sugar), maltose, water soluble artificial
sweeteners such as the soluble saccharin salts, i.e., sodium or
calcium saccharin salts, cyclamate salts dipeptide based
sweeteners, such a L-aspartic acid derived sweeteners, such as
L-aspartyl-L-phenylalaine methyl ester (aspartame). In general, the
effective amount of sweetener is utilized to provide the level of
sweetness desired for a particular composition, will vary with the
sweetener selected. This amount will normally be about 0.001% to
about 5% by weight of the composition. In some embodiments, the
sweetener is sodium saccharin and present at about 0.01% by weight
of the composition.
[0038] Optional breath freshening agents may be provided. Any
orally acceptable breath freshening agent can be used, including
without limitation zinc salts such as zinc gluconate, zinc citrate
and zinc chlorite, alpha-ionone and mixtures thereof. One or more
breath freshening agents are optionally present in a breath
freshening effective total amount.
[0039] Optionally, the composition may include a tartar control
(anticalculus) agent. Tartar control agents among those useful
herein include phosphates and polyphosphates (for example
pyrophosphates), polyaminopropanesulfonic acid (AMPS), polyolefin
sulfonates, polyolefin phosphates, diphosphonates such as
azacycloalkane-2,2-diphosphonates (e.g.,
azacycloheptane-2,2-diphosphonic acid), N-methyl
azacyclopentane-2,3-diphosphonic acid,
ethane-1-hydroxy-1,1-diphosphonic acid (EHDP) and
ethane-1-amino-1,1-diphosphonate, phosphonoalkane carboxylic acids
and salts of any of these agents, for example their alkali metal
and ammonium salts. Useful inorganic phosphate and polyphosphate
salts include monobasic, dibasic and tribasic sodium phosphates,
sodium tripolyphosphate, tetrapolyphosphate, mono-, di-, tri- and
tetrasodium pyrophosphates, sodium trimetaphosphate, sodium
hexametaphosphate and mixtures thereof, wherein sodium can
optionally be replaced by potassium or ammonium. Other useful
anticalculus agents include polycarboxylate polymers and polyvinyl
methyl ether/maleic anhydride (PVME/MA) copolymers, such as those
available under the Gantrez.TM. brand from ISP, Wayne, N.J.
[0040] In some embodiments, tartar control agent is present at a
concentration of from about 0.01 to 10%, by weight. In some
embodiments, the tartar control agent is present at a concentration
of about 1%, by weight. In some embodiments, the tartar control
agent also acts as a buffer. For example, in a phosphate buffer
system, sodium phosphate monobasic is present at a concentration of
from about 0.01 to about 5%, by weight and disodium phosphate is
present at a concentration of from about 0.01 to about 5%, by
weight, the precise ratio depending upon the other excipients in
the formulation and the desired pH.
[0041] Other optional additives include antimicrobial (e.g.,
antibacterial) agents. Any orally acceptable antimicrobial agent
can be used, including triclosan
(5-chloro-2-(2,4-dichlorophenoxy)phenol); zinc and stannous ion
sources; quaternary ammonium compounds such as cetylpyridinium
chloride (CPC); bisguanides such as chlorhexidine; and benzalkonium
chloride. A further illustrative list of useful antibacterial
agents is provided in U.S. Pat. No. 5,776,435 to Gaffar, et al. In
some embodiments, antimicrobial agent is present at a concentration
of from about 0.001 to about 1%, by weight. In some embodiments,
the antimicrobial agent is cetylpyridinium chloride. In some
embodiments, the cetylpyridinium chloride is present at a
concentration of about 0.05%, by weight.
[0042] Antioxidants are another class of optional additives. Any
orally acceptable antioxidant can be used, including butylated
hydroxyanisole (BHA), butylated hydroxytoluene (BHT), vitamin A,
carotenoids, vitamin E, flavonoids, polyphenols, ascorbic acid,
herbal antioxidants, chlorophyll, melatonin, and mixtures
thereof.
[0043] Also optional, saliva stimulating agent, useful for example
in amelioration of dry mouth may be included. Any orally acceptable
saliva stimulating agent can be used, including without limitation
food acids such as citric, lactic, malic, succinic, ascorbic,
adipic, fumaric, and tartaric acids, and mixtures thereof. One or
more saliva stimulating agents are optionally present in a saliva
stimulating effective total amount.
[0044] Optionally, an antiplaque (e.g., plaque disrupting) agent
may be included. Any orally acceptable antiplaque agent can be
used, including without limitation stannous, copper, magnesium and
strontium salts, dimethicone copolyols such as cetyl dimethicone
copolyol, papain, glucoamylase, glucose oxidase, urea, calcium
lactate, calcium glycerophosphate, strontium polyacrylates and
mixtures thereof.
[0045] Optional desensitizing agents include potassium citrate,
potassium chloride, potassium tartrate, potassium bicarbonate,
potassium oxalate, potassium nitrate, strontium salts, and mixtures
thereof. In some embodiments, a local or systemic analgesic such as
aspirin, codeine, acetaminophen, sodium salicylate or
triethanolamine salicylate can be used.
[0046] In some embodiments, the methods comprise the step of
rinsing the oral cavity with a composition as described herein. In
some embodiments, the shear thinning properties of the composition
increase the flow and thus the area covered when agitated within
the oral cavity. In some embodiments, a polymer film forms on the
surface of the oral cavity following discharge of the composition
which results in relief of dry mouth symptoms. In some embodiments,
5 ml or more of the composition is gargled. In some embodiments, 10
ml or more is used. In some embodiments, 10-50 ml is used. In some
embodiments, 15-25 ml or more is used. In some embodiments, 15 ml
or more is used. In some embodiments, the individual gargles with
the composition multiple times per day. In some embodiments, the
individual gargles with the composition on multiple days. In some
embodiments, the individual gargles with the composition every 4 to
6 hours up to 6 times per day.
[0047] As used throughout, ranges are used as shorthand for
describing each and every value that is within the range. Any value
within the range can be selected as the terminus of the range. In
addition, all references cited herein are hereby incorporated by
referenced in their entireties.
[0048] In the event of a conflict in a definition in the present
disclosure and that of a cited reference, the present disclosure
controls.
[0049] Unless otherwise specified, all percentages and amounts
expressed herein and elsewhere in the specification should be
understood to refer to percentages by weight. The amounts given are
based on the active weight of the material.
EXAMPLES
Example 1
[0050] The objective is to provide a viscoelastic mouthwash
containing a polymer system plus an active (arginine, preferably
with fluoride) for superior protection of enamel against acid
induced demineralization. Mouthwash formulations are prepared with
the following ingredients:
TABLE-US-00002 TABLE 2 Concentration Mouthwash 1: Ingredients (%
wt/wt) Water 71.05 Humectants 17.5 Surfactant 1 Sodium phosphate
monobasic 1 Disodium phosphate 0.15 Preservative 0.5 Flavor 0.2
Carboxymethyl Cellulose 0.083 Xanthan Gum 0.083 Acrylate co-polymer
0.05 Sodium fluoride 0.02 Arginine (Arg HCO.sub.3) 1.3 Sweetener
0.01 Cetylpyridinium chloride 0.05
TABLE-US-00003 TABLE 3 Concentration Mouthwash 2: Ingredients (%
wt/wt) Water 72.35 Humectants 17.5 Surfactant 1 Sodium phosphate
monobasic 1 Disodium phosphate 0.15 Preservative 0.5 Flavor 0.2
Carboxymethyl Cellulose 0.083 Xanthan Gum 0.083 Acrylate co-polymer
0.05 Sodium fluoride 0.05 Arginine (as L-Arginine) 0.8 Sweetener
0.01 Cetylpyridinium chloride 0.05
TABLE-US-00004 TABLE 4 Theoretical Mouthwash 3: Ingredients Weight
(%) Water 71.22 Sorbitol (70% Soln.) 10 Glycerin 7.5 Propylene
glycol 7 L-Arginine 0.8 Poloxamer 407 1 Monobasic sodium phosphate
1 FD&C GREEN NO. 3 0.000375 Cetylpyridinium chloride 0.05
Sodium benzoate 0.5 Flavor 0.2 Sodium phosphate dibasic 0.15 Sodium
saccharin 0.01 Xanthan gum 0.083 Sodium CMC 0.083 Polyacrylate
copolymer 0.05 Trimethyl glycine 0.3 Sodium fluoride 0.05
Example 2
[0051] Exemplary compositions of the present invention can be
prepared according to the following procedure:
[0052] Add approximately 1/3 of the water to a small vessel and
slowly add in the acrylate co-polymer with strong mixing.
[0053] Add remaining water to the main mix tank.
[0054] Add the Poloxomer 407 and mix until fully dissolved.
[0055] Add the appropriate amount of sorbitol.
[0056] Add the sodium phosphate monobasic, sodium benzoate,
anhydrous sodium phosphate dibasic, sodium saccharin, Betafin BP20,
and L-Arginine and mix each in before adding the next.
[0057] Add the CPC and dye. Mix for 10 minutes to ensure the entire
batch is completely solubilized.
[0058] Slurry the xanthan gum and CMC into the propylene
glycol.
[0059] Add acrylate co-polymer and water mixture to the main mix
tank.
[0060] Add xanthan gum and CMC slurry to the main mix tank and mix
for 15 minutes.
[0061] Add flavor and mix for 5 minutes.
Example 3
[0062] The tri-polymer mouthwash formulations of Example 1 are
evaluated for their rheological properties, in comparison with
water, saliva, and three commercial mouthwashes. The three
commercial mouthwashes are a simple fluoride-rinse type mouthwash
(comparative formulation 1), a polymer based high fluoride
mouthwash (comparative formulation 2), and a mouthwash having a
conventional polymer system different from that described in this
case (mouthwash 3). The rheological properties of the formulations
are quantified using a stress controlled AR2000ex rheometer (TA
Instruments) and a cuette type geometry. A flow curve is generated
and fit to a power law model to quantify the flow rate index , n. A
strain sweep is conducted to quantify the elastic modulus, G' and
the loss modulus, G''. The results are described in Table 5
(below).
TABLE-US-00005 TABLE 5 G' G'' Key (dyn/ (dyn/ k Sample Name
Ingredients cm2) cm2) G'/G'' (cps) n Newtonian Water 0.02 0.23 0.09
1.1 1.0 Fluid Example Viscoelastic Natural saliva 21.24 4.79 4.43
88.30 0.41 Fluid Example Tri-Polymer Polymer 8.25 5.57 1.48 163.5
0.50 Mouthwash 1 Network + 90 ppm Fluoride + Arginine Tri-Polymer
Polymer 3.38 5.04 0.67 153.7 0.60 Mouthwash 2 Network + 225 ppm
Fluoride + Arginine Comparative 225 ppm 0.06 0.69 0.09 5.35 1.00
Example 1 fluoride Comparative Polymer + 0.22 1.62 0.14 20.84 0.91
Example 2 400 ppm Fluoride Comparative Polymer + 0.52 3.16 0.17
19.92 1.00 Example 3 225 ppm Fluoride + Arginine
[0063] The data described in Table 5 (above) demonstrates that
compositions of the present invention are viscoelastic (more like
saliva), whereas the comparative examples are Newtonian (more like
water).
Example 4
[0064] The tri-polymer mouthwashes are then compared with the
commercial mouthwashes for their ability to protect against enamel
loss. Enamel loss for the tri-polymer mouthwash prototypes are
compared to water and the three commercial examples using an in
vitro methodology based on the protocol published by S. M. Hooper,
R. G. Newcombe, R. Faller, S. Eversole, M. Addy, N. X. West,
Journal of Dentistry, 35 (2007), 476-481. Each formulation is
tested with 4 to 6 replicates to obtain statistically meaningful
results.
[0065] Bovine incisors are cleaned and sterilized with 70% alcohol.
Each specimen is embedded in epoxy resin using a Teflon mold to
form a 20 mm.times.10 mm.times.5 mm block. The enamel surface is
ground using 600 and 1200 grit silicon carbide paper consecutively
to achieve a shiny, flat surface. Each enamel surface is masked
with tape, leaving only the center area (.about.0.5 mm wide)
exposed. The masked enamel blocks are pre-etched with a 5% citric
acid solution for 30 sec to create a pre-existing (incipient)
lesion. All enamel samples are kept in artificial saliva at
37.degree. C. for at least 12 hours prior to experimentation. The
artificial saliva contained the following ingredients in 1000 mL of
deionized water: 25 g mucin from porcine stomach, 466 mg
NH.sub.4Cl, 420 mg CaCl.sub.2.H.sub.2O, 86 mg MgCl.sub.2.6H.sub.2O,
2314 mg KCl, 708 mg KH.sub.2PO.sub.4, 444 mg KCNS, 1070 mg
NaHCO.sub.3, 750 mg NaH.sub.2PO.sub.4, 26 mg Sodium
Citrate.2H.sub.2O, 50 mg Albumin (BSA), 346 mg Urea, and 900 mg
Glycine.
[0066] The erosion study is conducted through a cyclic
de-mineralization and re-mineralization procedure. Each enamel
substrate is treated with the assigned MW formulation or
no-treatment H.sub.2O control for 1 min in the morning, and then
de-mineralized twice for 2 min using a 1% citric acid solution
titrated to pH 3.8 with NaOH. The same procedure is repeated in the
afternoon and this daily treatment regimen is repeated for 5 days.
Except during de-mineralizations and MW treatments, the enamel
substrates are always stored in artificial saliva at 37.degree. C.
Profilometry is used to quantify the enamel loss induced by acid
exposure by measuring the step heights of the unmasked center
relative to the masked regions. Enamel loss is computed using the
step height difference before and after the cycling study.
[0067] The usage of the viscoelastic tri-polymer based prototypes
results in a substantial and surprising decrease in enamel loss
compared to that seen using the commercial comparator formulations,
as seen in Table 6 (below).
TABLE-US-00006 TABLE 6 Sample Name Key Ingredients Enamel Loss
Water Water 0.4443 Tri-Polymer Polymer Network + 90 ppm 0.2258
Mouthwash 1 Fluoride + Arginine Tri-Polymer Polymer Network + 225
ppm 0.2165 Mouthwash 3 Fluoride + Arginine Comparative 225 ppm
fluoride 0.3885 Example 1 Comparative Polymer + 400 ppm Fluoride
0.4969 Example 2 Comparative Polymer + 225 ppm Fluoride + 0.3877
Example 3 Arginine
[0068] The data described in Table 6 (above) demonstrates that
compositions of the present invention unexpectedly provide a step
height difference of less than 0.25 microns, when evaluated using
the Hooper protocol described herein; whereas similarly formulated
compositions which do not contain the inventive combinations
described herein are unable to provide the same level of protection
against enamel loss.
* * * * *